1. Gastric lymphoma: changing role of surgery
Joint Hospital Surgical Grand Round
Dr Bonita HK Mark
RHTSK

2. Gastric lymphoma What is gastric lymphoma?
Why do we need to know about it?
What is the evidence in literature?
How to treat?
When to operate / not to operate?

3. Lymphoma Extranodal Nodal MALT Splenic GI Tract Others
Hodgkin’s Non-Hodgkin’s
Extranodal Nodal
MALT Splenic
GI Tract Others

4. Working formulation (NCI 1982)
Low grade
Intermediate grade
High grade
Miscellaneous
Small lymphocytic
Follicular large cell
Diffuse large cell immunoblastic
Composite
Follicular small cell
Diffuse small cleaved cell
Lymphoblastic
Mycosis fungoides
Follicular mixed small & large
Diffuse mixed small & large
Small cell (Burkitt’s or non-Burkitt’s)
Others
Diffuse large cell

5. Revised European-American Lymphoma (REAL) (WHO 1993)
B-cell lymphoma
Lymphoblastic
Small lymphocytic
Lymphoplasmacytoid
Mantle-cell
Follicular center (follicular, diffuse, small)
Marginal-zone (nodal, extranodal, splenic)
Diffuse large B-cell
Burkitt’s / Burkitt-like
T cell lymphoma
Lymphoblastic
Mycosis fungoides/ sezary syndrome
Peripheral T-cell

6. MALT lymphoma MALT (mucosa associated lymphoid tissue) lymphoma
First described in 1983
Extra-nodal marginal zone B-cell lymphoma
Indolent (low grade)
Most common in GI tract (50%)
Stomach mostly involved (50-70% of GI MALT)
4% primary gastric tumours
40-50% primary gastric lymphomas

7. MALT lymphoma

8. MALT lymphoma – clinical features
Brooks et al (n=56)
Rackner et al (n=33)
Hockey et al (n=153)
Pain
78%
67%
70%
Weight loss
40%
39%
15%
Nausea
14%
12%
Vomiting
32%
14.4%
Fatigue 4%
21%
3.3%
Night sweat 2%
Dysphagia 9%
4.6%
Bleeding
20%
24%
8.5%
Obstruction 0%
Anorexia
10%
6.5%
Perforation 3%
Mass
0.7%
Lymphadenopathy

9. MALT lymphoma - diagnosis
Upper endoscopy
Biopsy of suspicious area
Ulceration
Nodular mass
Diffuse infiltration
Antral biopsy for H pylori
Endoscopic ultrasound
Depth of tumour invasion
Perigastric LN enlargement
CT chest, abdomen and pelvis/ PET scan
Bone marrow biopsy

10. MALT lymphoma - endoscopy

11. MALT lymphoma - endoscopy

12. MALT lymphoma – endoscopic US
Serosal involvement
Superficial (submucosal) involvement

13. MALT lymphoma – endoscopic US
Perigastric LN enlargement

14. MALT lymphoma - staging
Musshoff’s modification of Ann Arbor system
Stage
Definition IE
Lymphoma limited to the stomach
IIE₁
Involvement of stomach and contiguous LN
IIE₂
Involvement of stomach and noncontiguous subdiaphragmatic LN
III
Involvement of stomach and LN on both sides of diaphragm IV
Haematogenous spread (stomach and one or more extra-lymphatic organs or tissues)

15. H pylori eradication therapy
Low grade MALT lymphoma: stage I or II disease with slow progression
H pylori in 90% gastric MALT lymphoma
2/3 lymphoma regresses after eradication
Prognosis good: 10-year survival 80-90%

16. H pylori eradication therapy
Annals of Surgery, Vol 240(1), July 2004, p28-37

17. Predictive factors for poor response to H pylori eradication therapy
Perigastric LN involvement (stage II₁)
0% with stage II vs. 79% with stage I
(Multicentre French study, Gut 2001; 48: )
33% LN +ve vs. 76% LN –ve
(Am J Gastroenterology 2002; 97: )
A t (11:18) chromosomal translocation
review of 111 patients by Liu et al: 73% vs. 4% (Gastroenterology 2002; 122: )
H pylori -ve

18. What is the best Rx modality?

19. Implications to surgeons

21. Low grade vs high grade

22. Early vs advanced disease

23. Literature review

24. Surgery for gastric lymphoma
Brands et al reviewed 100 papers analyzing 3157 patients with all stages of gastric lymphoma
Treated from 1974 to 1995
The overall survival during that time period ↑from 37% to 87%.

25. Rev Esp Enferm Dig 2006; 98:

26. Review article
Ann Surg 2004; 240:28-37

28. Perforation? Haemorrhage?
Survival rate?
Perforation? Haemorrhage?
Recurrence?

29. Chemotherapy/RT without surgery
Aviles et al in 1991
52 patients with stage I or II gastric lymphoma
Prospectively randomized
Chemo vs. surgery + chemo
Relapse-free survival and overall survival were equivalent
Five-year overall survival 75% in both groups
Milan series by Ferreri et al in 1999
83 patients with stage I or II high-grade gastric lymphoma
Reviewed retrospectively
Chemo/ chemo + RT vs. surgery +/- adjuvant
No difference in survival
5-year survival of 82%, 10-year survival of 64% (non-surgical)

30. Chemotherapy/RT without surgery
German Multicenter Study Group by Koch et al in 2001
Prospective nonrandomized study
185 patients with stage I or II
Surgery (gastrectomy + RT or + chemo +RT) :106
Non-surgery (RT or chemo +RT): 79
No significant difference in survival (overall 5-year survival rate: 82% vs. 84%)

31. Chemotherapy/RT without surgery
Aviles et al
No perforation
Bleeding: 3 (non-surgical) vs. 2 (surgical)
German Multicenter Study Group by Koch et al
Perforation: 1 (non-surgical) vs. none (surgical)
No bleeding

32. Chemotherapy/RT without surgery
German Multicenter Study Group by Koch et al
6 recurred after surgical Rx: 3 systemically, 3 loco-regionally
7 recurred after non-surgical Rx: all locally
Ferreri et al
17/62 recurred after surgical Rx: 2 locally and 15 systemically
4/19 complete responders recurred: 2 locally and 2 systemically
Recurrence patterns may differ:
Surgical: tend to recur systemically
Non-surgical: more local recurrence

33. Retrospective review
J Formos Med Assoc 2006; 105(3):

34. Retrospective review Objective: Methods:
To evaluate the outcome of PGL (except MALT lymphoma) treated with chemo alone or surgery followed by chemo
Methods:
55 PGL patients (MALT lymphoma excluded)
Localized 32 (IE 15 + IIE 17)
Advanced 23
Chemo alone vs. Combination (surgery + chemo)

35. Retrospective review Results: Complete remission no sig. difference:
Chemo: 84.2%
Combination: 92.3%
5-year overall survival no sig. difference:
Chemo: 73.4%
Combination: 87.5%
5-year disease-free survival no sig. difference:
Chemo: 68.4%
Combination: 84.6%

36. Retrospective review Post-chemo life-threatening haemorrhage:
5/32 (15.6%) in localized group (stage IE/IIE1)
4 chemo + 1 combination
9/23 in advanced group
6 chemo + 3 combination
5 of them developed perforation and died
Grade 3-4 neutropenia:
Chemo: 13.2
Combination: 17.6%
Thrombocytopenia:
Chemo: 2.6%
Combination: 5.9%

37. Retrospective review - conclusion
Clinical outcome of localized PGL treated by chemo alone is comparable to that treated by combination therapy
In terms of : tumour response, disease-free survival and overall survival
Bulky tumours: tumour bleeding/perforation
Debulking surgery followed by chemo can offer better tumour control / ↓complication

38. In summary

39. Gastric lymphoma Rx MALT lymphoma High-grade (non-MALT)
H pylori eradication therapy
High-grade (non-MALT)
Chemo +/-RT
Surgery
For bulky tumour to prevent bleeding/perforation
For local residual disease post chemo/RT
For palliation of symptoms like obstruction

40. THANK YOU!

41. Some additional information
For discussion

42. Gastric lymphoma grading

43. International prognostic index
Age: <60 years vs. >60 years
Serum LDH: normal vs. elevated
Performance status: 0 or 1 vs. 2-4
Stage: stage I / II vs. stage III / IV
Extranodal site involvement: 0 or 1 vs. 2-4

44. Performance status Grade Description
Fully active, able to carry on all pre-disease performance without restriction 1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours 3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 5
Dead

45. Time interval for response
4 weeks to 12 months
Subgroup with high success rate (confined to gastric wall, no translocation, no LN): await for 12 months
Subgroup with low success rate: consider other therapy earlier e.g. 3-6 months

46. Retrospective study

47. Retrospective study Objective:
To assess whether surgical excision is still a valid therapeutic option
Patients and method:
A retrospective study
69 consecutive patients stage IE-IIE
65 (94.2%) gastrectomy
Mean age: 62.6 years (28-85)

48. Retrospective study 5-year survival probability (SP): 87.93%
Rev Esp Enferm Dig 2006; 98(3):

49. Retrospective study Statistical analysis: Ann Arbor stage:
Gastric wall invasion, H. pylori , margin:
Histological type: borderline significance
(p = 0.056)

50. Retrospective study
Rev Esp Enferm Dig 2006; 98(3):

51. Retrospective study - conclusion
Good long-term survival (> 87% after 5 years)
No prognostic value in surgical margin involvement.
Radical excision (R0), according to the criteria used in carcinomas, was not associated with a significantly longer survival than excisions leaving microscopic residual tumor (R1).